Molecular studies have recently identified two families of taste receptors. The T1r receptors recognize some sweet or amino acid stimuli, whereas T2r receptors are implicated for the detection of bitter-tasting ligands. The expression patterns of these receptors have invigorated interest in the idea that sweet and bitter taste are represent by dedicated coding channels in the nervous system; however, sweet- or bitter-responsive central gustatory neurons vary in their sensitivities to stimuli of other taste qualities, which questions whether input from T1r or T2r receptors is segregated to specifically-tuned cells in the brain. Experiments in this application involve electrophysiological measurement of taste responses in single neurons in the brain stem in mice with targeted manipulation of the gene Sac or Soa. Sac influences preference for sweets in mammals and encodes the sweet taste receptor T1r3. In Aim 1, we will measure differences in neural responding to sweet-tasting stimuli between mice engineered to carry a non-functional Sac allele (T1r3 knockout mice) and wild-type mice. Soa regulates sensitivity to bitter-tasting stimuli and co-localizes with the T2r bitter taste receptor genes. In Aim 2, neural responses to bitter-tasting stimuli will be compared between two strains of mice that genetically differ at only the gene Soa. These studies will identify categories of neurons in which taste responses to sweet or bitter stimuli are influenced by the manipulation of these genes, revealing cell types that receive input from the receptor products of Sac or Soa. The specificity of these identified cell types will be evaluated to determine if they could function as coding channels for the taste qualities of sweet or bitter or if their response properties are conducive to a different coding strategy. Results will bear on how taste information mediated by the receptors encoded by Sac and Soa is represented by neural activity. These experiments will test the hypothesis that genetic variation at Sac or Soa influences central gustatory neurons that are variably sensitive to stimuli of different taste qualities. Moreover, these experiments will identify categories of gustatory neurons in the brain that are fundamental to the neural substrates by which Sac and Soa influence behavioral responding towards taste stimuli, which will provide insight into the neurobiological mechanisms by which these genes control taste preference. Taste preferences guide dietary choices leading to many health problems in humans, such as cancer, obesity, and diabetes.

R03DC008194

2006-04-01

2010-03-31